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Spatial constraints dictate glial territories at murine neuromuscular junctions.

Brill MS, Lichtman JW, Thompson W, Zuo Y, Misgeld T - J. Cell Biol. (2011)

Bottom Line: Adult terminal SCs are arranged in static tile patterns, whereas young SCs dynamically intermingle.The mechanism of developmental glial segregation appears to be spatial competition, in which glial-glial and axonal-glial contacts constrain the territory of single SCs, as shown by four types of experiments: (1) laser ablation of single SCs, which led to immediate territory expansion of neighboring SCs; (2) axon removal by transection, resulting in adult SCs intermingling dynamically; (3) axotomy in mutant mice with blocked axon fragmentation in which intermingling was delayed; and (4) activity blockade, which had no immediate effects.In summary, we conclude that glial cells partition synapses by competing for perisynaptic space.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Integrated Protein Science Munich at the Institute of Neuroscience, Technische Universität München, 80802 Munich, Germany.

ABSTRACT
Schwann cells (SCs), the glial cells of the peripheral nervous system, cover synaptic terminals, allowing them to monitor and modulate neurotransmission. Disruption of glial coverage leads to axon degeneration and synapse loss. The cellular mechanisms that establish and maintain this coverage remain largely unknown. To address this, we labeled single SCs and performed time-lapse imaging experiments. Adult terminal SCs are arranged in static tile patterns, whereas young SCs dynamically intermingle. The mechanism of developmental glial segregation appears to be spatial competition, in which glial-glial and axonal-glial contacts constrain the territory of single SCs, as shown by four types of experiments: (1) laser ablation of single SCs, which led to immediate territory expansion of neighboring SCs; (2) axon removal by transection, resulting in adult SCs intermingling dynamically; (3) axotomy in mutant mice with blocked axon fragmentation in which intermingling was delayed; and (4) activity blockade, which had no immediate effects. In summary, we conclude that glial cells partition synapses by competing for perisynaptic space.

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Immature SCs are highly dynamic, whereas adult SCs are static. (A–F) Confocal time-lapse microscopy of young (A–C) and adult (D–F) SC-GFP terminal SCs in nerve–muscle explants. (A and D) Sequentially bleached young (A) and adult (D) NMJs with pseudocolored terminal and axonal SCs. (B and E) NMJ labeled for axons (thy1-Membow13) and SCs (white). (C and F) Time-lapse recordings over ∼2 h (areas boxed in A and D). Immature terminal SCs were highly dynamic (C; arrowheads), whereas only minor growth or retraction was observed in the adult (F), especially at contact sites with neighboring cells (arrowheads). (G and H) Quantitative analysis of SC dynamism. (G) Example of individual young and adult terminal SC showing mean area covered (cyan) and maximum territory covered (white outline). (H) Quantification of explored territory within 1 h (young: 31.4 ± 2%, n = 24 individual SCs, eight triangularis sterni explants vs. adult: 10.2 ± 1%, n = 14 individual SCs, six triangularis sterni explants; values are normalized to terminal SC size; *, P < 0.001 using a t test; data are represented as the mean of SCs + SEM). (I and J) Territory exploration plotted over a period of 1 h for young (I) and adult (J) terminal SCs (territory difference per 10 min plotted; bars on the right show the mean ± SD; total territories stay stable for 1 h; change −0.45 µm2 for young and −0.28 µm2 for adult terminal SCs, shown normalized to SC size in the figure). The timers shown represent hours/minutes. Bars, 5 µm.
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fig2: Immature SCs are highly dynamic, whereas adult SCs are static. (A–F) Confocal time-lapse microscopy of young (A–C) and adult (D–F) SC-GFP terminal SCs in nerve–muscle explants. (A and D) Sequentially bleached young (A) and adult (D) NMJs with pseudocolored terminal and axonal SCs. (B and E) NMJ labeled for axons (thy1-Membow13) and SCs (white). (C and F) Time-lapse recordings over ∼2 h (areas boxed in A and D). Immature terminal SCs were highly dynamic (C; arrowheads), whereas only minor growth or retraction was observed in the adult (F), especially at contact sites with neighboring cells (arrowheads). (G and H) Quantitative analysis of SC dynamism. (G) Example of individual young and adult terminal SC showing mean area covered (cyan) and maximum territory covered (white outline). (H) Quantification of explored territory within 1 h (young: 31.4 ± 2%, n = 24 individual SCs, eight triangularis sterni explants vs. adult: 10.2 ± 1%, n = 14 individual SCs, six triangularis sterni explants; values are normalized to terminal SC size; *, P < 0.001 using a t test; data are represented as the mean of SCs + SEM). (I and J) Territory exploration plotted over a period of 1 h for young (I) and adult (J) terminal SCs (territory difference per 10 min plotted; bars on the right show the mean ± SD; total territories stay stable for 1 h; change −0.45 µm2 for young and −0.28 µm2 for adult terminal SCs, shown normalized to SC size in the figure). The timers shown represent hours/minutes. Bars, 5 µm.

Mentions: Immature terminal SCs rapidly formed and retracted cytoplasmic protrusions (Fig. 2 [A–C] and Video 1). These protrusions extended within the synapse, exploring the territory covered by a neighboring SC but also areas beyond the synaptic border. Similar outgrowth of axons has been described for young NMJs (Walsh and Lichtman, 2003), but when we concomitantly imaged axons and SCs at immature NMJs, no clear relationship between their protrusions was apparent (Video 1). Terminal SCs extended processes along the axon that innervates the synapse (unpublished data). At the same time, axonal SCs explored synaptic territory (Fig. S3), suggesting that at early developmental ages, there is no barrier to SC growth across the synaptic entry point.


Spatial constraints dictate glial territories at murine neuromuscular junctions.

Brill MS, Lichtman JW, Thompson W, Zuo Y, Misgeld T - J. Cell Biol. (2011)

Immature SCs are highly dynamic, whereas adult SCs are static. (A–F) Confocal time-lapse microscopy of young (A–C) and adult (D–F) SC-GFP terminal SCs in nerve–muscle explants. (A and D) Sequentially bleached young (A) and adult (D) NMJs with pseudocolored terminal and axonal SCs. (B and E) NMJ labeled for axons (thy1-Membow13) and SCs (white). (C and F) Time-lapse recordings over ∼2 h (areas boxed in A and D). Immature terminal SCs were highly dynamic (C; arrowheads), whereas only minor growth or retraction was observed in the adult (F), especially at contact sites with neighboring cells (arrowheads). (G and H) Quantitative analysis of SC dynamism. (G) Example of individual young and adult terminal SC showing mean area covered (cyan) and maximum territory covered (white outline). (H) Quantification of explored territory within 1 h (young: 31.4 ± 2%, n = 24 individual SCs, eight triangularis sterni explants vs. adult: 10.2 ± 1%, n = 14 individual SCs, six triangularis sterni explants; values are normalized to terminal SC size; *, P < 0.001 using a t test; data are represented as the mean of SCs + SEM). (I and J) Territory exploration plotted over a period of 1 h for young (I) and adult (J) terminal SCs (territory difference per 10 min plotted; bars on the right show the mean ± SD; total territories stay stable for 1 h; change −0.45 µm2 for young and −0.28 µm2 for adult terminal SCs, shown normalized to SC size in the figure). The timers shown represent hours/minutes. Bars, 5 µm.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3198169&req=5

fig2: Immature SCs are highly dynamic, whereas adult SCs are static. (A–F) Confocal time-lapse microscopy of young (A–C) and adult (D–F) SC-GFP terminal SCs in nerve–muscle explants. (A and D) Sequentially bleached young (A) and adult (D) NMJs with pseudocolored terminal and axonal SCs. (B and E) NMJ labeled for axons (thy1-Membow13) and SCs (white). (C and F) Time-lapse recordings over ∼2 h (areas boxed in A and D). Immature terminal SCs were highly dynamic (C; arrowheads), whereas only minor growth or retraction was observed in the adult (F), especially at contact sites with neighboring cells (arrowheads). (G and H) Quantitative analysis of SC dynamism. (G) Example of individual young and adult terminal SC showing mean area covered (cyan) and maximum territory covered (white outline). (H) Quantification of explored territory within 1 h (young: 31.4 ± 2%, n = 24 individual SCs, eight triangularis sterni explants vs. adult: 10.2 ± 1%, n = 14 individual SCs, six triangularis sterni explants; values are normalized to terminal SC size; *, P < 0.001 using a t test; data are represented as the mean of SCs + SEM). (I and J) Territory exploration plotted over a period of 1 h for young (I) and adult (J) terminal SCs (territory difference per 10 min plotted; bars on the right show the mean ± SD; total territories stay stable for 1 h; change −0.45 µm2 for young and −0.28 µm2 for adult terminal SCs, shown normalized to SC size in the figure). The timers shown represent hours/minutes. Bars, 5 µm.
Mentions: Immature terminal SCs rapidly formed and retracted cytoplasmic protrusions (Fig. 2 [A–C] and Video 1). These protrusions extended within the synapse, exploring the territory covered by a neighboring SC but also areas beyond the synaptic border. Similar outgrowth of axons has been described for young NMJs (Walsh and Lichtman, 2003), but when we concomitantly imaged axons and SCs at immature NMJs, no clear relationship between their protrusions was apparent (Video 1). Terminal SCs extended processes along the axon that innervates the synapse (unpublished data). At the same time, axonal SCs explored synaptic territory (Fig. S3), suggesting that at early developmental ages, there is no barrier to SC growth across the synaptic entry point.

Bottom Line: Adult terminal SCs are arranged in static tile patterns, whereas young SCs dynamically intermingle.The mechanism of developmental glial segregation appears to be spatial competition, in which glial-glial and axonal-glial contacts constrain the territory of single SCs, as shown by four types of experiments: (1) laser ablation of single SCs, which led to immediate territory expansion of neighboring SCs; (2) axon removal by transection, resulting in adult SCs intermingling dynamically; (3) axotomy in mutant mice with blocked axon fragmentation in which intermingling was delayed; and (4) activity blockade, which had no immediate effects.In summary, we conclude that glial cells partition synapses by competing for perisynaptic space.

View Article: PubMed Central - HTML - PubMed

Affiliation: Center for Integrated Protein Science Munich at the Institute of Neuroscience, Technische Universität München, 80802 Munich, Germany.

ABSTRACT
Schwann cells (SCs), the glial cells of the peripheral nervous system, cover synaptic terminals, allowing them to monitor and modulate neurotransmission. Disruption of glial coverage leads to axon degeneration and synapse loss. The cellular mechanisms that establish and maintain this coverage remain largely unknown. To address this, we labeled single SCs and performed time-lapse imaging experiments. Adult terminal SCs are arranged in static tile patterns, whereas young SCs dynamically intermingle. The mechanism of developmental glial segregation appears to be spatial competition, in which glial-glial and axonal-glial contacts constrain the territory of single SCs, as shown by four types of experiments: (1) laser ablation of single SCs, which led to immediate territory expansion of neighboring SCs; (2) axon removal by transection, resulting in adult SCs intermingling dynamically; (3) axotomy in mutant mice with blocked axon fragmentation in which intermingling was delayed; and (4) activity blockade, which had no immediate effects. In summary, we conclude that glial cells partition synapses by competing for perisynaptic space.

Show MeSH
Related in: MedlinePlus